tbuckley/cabot-search huggingface dataset:
Prediction of Psoriatic Arthritis in Patients With Psoriasis Using <scp>DNA</scp> Methylation Profiles
Authors: Omar F. Cruz‐Correa, Remy A. Pollock, Rohan Machhar, Dafna D. Gladman
Journal: Arthritis & Rheumatology (2023)

Psoriatic arthritis (PsA) is an immune-mediated inflammatory arthritis, associated with psoriasis, that significantly increases morbidity and mortality risk. We currently lack the means of predicting which patients with psoriasis will develop PsA, and a large number of patients remain undiagnosed. Regulation of gene expression through DNA methylation can potentially trigger and maintain PsA pathophysiological processes. We aimed to identify DNA methylation markers that can predict which patients with psoriasis will develop PsA prior to the onset of musculoskeletal symptoms.Genome-wide DNA methylation was assessed in blood samples from patients with psoriasis who went on to develop arthritis (converters) and patients with psoriasis who did not (biologic naive, matched for age, sex, psoriasis duration, and duration of follow-up). Methylation differences between converters and nonconverters were identified by a multivariate linear regression model including clinical covariates (age, sex, body mass index, smoking). Predictive performance of methylation markers was assessed by developing support vector machine classification models with and without the addition of clinical variables.We identified a set of 36 highly relevant methylation markers (false discovery rate: adjusted P < 0.05 and a minimum change in methylation of 0.05) across 15 genes and several intergenic regions. A classification model relying on these markers identified converters and nonconverters with an area under the receiver operating characteristic curve of 0.9644.This study shows that DNA methylation patterns at an early stage of psoriatic disease can distinguish between patients who will develop PsA from those who will not during the same follow-up.
Computer Vision Analysis of Rheumatoid Arthritis Synovium Reveals Lymphocytic Inflammation Is Associated With Immunoglobulin Skewing in Blood
Authors: Damon Frezza, Edward DiCarlo, Caryn Hale, Daniel Ramirez, Bella Mehta, David Slater, Saimun Habib, Mayu O. Frank, Edoardo Spolaore, Melanie H. Smith, Laura Donlin, Susan Goodman, James R. Thompson, Dana E. Orange
Journal: Arthritis & Rheumatology (2023)

Objective We sought to develop computer vision methods to quantify aggregates of cells in synovial tissue and compare these with clinical and gene expression parameters. Methods We assembled a computer vision pipeline to quantify five features encompassing synovial cell density and aggregates and compared these with pathologist scores, disease classification, autoantibody status, and RNA expression in a cohort of 156 patients with rheumatoid arthritis (RA) and 149 patients with osteoarthritis (OA). Results All five features were associated with pathologist scores of synovial lymphocytic inflammation ( P &lt; 0.0001). Three features that related to the cells per unit of tissue were significantly increased in patients with both seronegative and seropositive RA compared with those with OA; on the other hand, aggregate features (number and diameter) were significantly increased in seropositive, but not seronegative, RA compared with OA. Aggregate diameter was associated with the gene expression of immunoglobulin heavy‐chain genes in the synovial tissue. Compared with blood, synovial immunoglobulin isotypes were skewed from IGHM and IGHD to IGHG3 and IGHG1 . Further, patients with RA with high levels of lymphocytic infiltrates in the synovium demonstrated parallel skewing in their blood with a relative decrease in IGHGM ( P &lt; 0.002) and IGHD ( P &lt; 0.03) and an increase in class‐switched immunoglobulin genes IGHG3 ( P &lt; 0.03) and IGHG1 ( P &lt; 0.002). Conclusion High‐resolution automated identification and quantification of synovial immune cell aggregates uncovered skewing in the synovium from naïve IGHD and IGHM to memory IGHG3 and IGHG1 and revealed that this process is reflected in the blood of patients with high inflammatory synovium. image
Health nationalism in Aotearoa New Zealand during COVID-19: problems for global health equity
Authors: John A. Crump, Patrick Vakaoti, Michael Moore-Jones, Lena Tan, Christina R. Ergler, Elizabeth Fenton, Emma M. R. Anderson, Philip J. Bremer, Katrina J. Sharples, Tony Walls, Miguel E. Quiñones-Mateu, Komathi Kolandai, Jacqui Hadingham, Philip C. Hill, Stephen Knowles
Journal: Nature Medicine (2023)
Cognitive effects of Lewy body pathology in clinically unimpaired individuals
Authors: Sebastian Palmqvist, Marcello Rossi, Sara Hall, Corinne Quadalti, Niklas Mattsson-Carlgren, Sofia Dellavalle, Pontus Tideman, Joana B. Pereira, Maria H. Nilsson, Angela Mammana, Shorena Janelidze, Simone Baiardi, Erik Stomrud, Piero Parchi, Oskar Hansson
Journal: Nature Medicine (2023)

Abstract α-Synuclein aggregates constitute the pathology of Lewy body (LB) disease. Little is known about the effects of LB pathology in preclinical (presymptomatic) individuals, either as isolated pathology or coexisting with Alzheimer’s disease (AD) pathology (β-amyloid (Aβ) and tau). We examined the effects of LB pathology using a cerebrospinal fluid α-synuclein-seed amplification assay in 1,182 cognitively and neurologically unimpaired participants from the BioFINDER study: 8% were LB positive, 26% Aβ positive (13% of those were LB positive) and 16% tau positive. LB positivity occurred more often in the presence of Aβ positivity but not tau positivity. LB pathology had independently negative effects on cross-sectional and longitudinal global cognition and memory and on longitudinal attention/executive function. Tau had cognitive effects of a similar magnitude, but these were less pronounced for Aβ. Participants with both LB and AD (Aβ and tau) pathology exhibited faster cognitive decline than those with only LB or AD pathology. LB, but not AD, pathology was associated with reduced sense of smell. Only LB-positive participants progressed to clinical LB disease over 10 years. These results are important for individualized prognosis, recruitment and choice of outcome measures in preclinical LB disease trials, but also for the design of early AD trials because &gt;10% of individuals with preclinical AD have coexisting LB pathology.
Roadmap on the use of artificial intelligence for imaging of vulnerable atherosclerotic plaque in coronary arteries
Authors: Bernhard Föllmer, Michelle C. Williams, Damini Dey, Armin Arbab-Zadeh, Pál Maurovich-Horvat, Rick H. J. A. Volleberg, Daniel Rueckert, Julia A. Schnabel, David E. Newby, Marc R. Dweck, Giulio Guagliumi, Volkmar Falk, Aldo J. Vázquez Mézquita, Federico Biavati, Ivana Išgum, Marc Dewey
Journal: Nature Reviews Cardiology (2023)
Author Correction: Understanding and combatting misinformation across 16 countries on six continents
Authors: Antonio A. Arechar, Jennifer Allen, Adam J. Berinsky, Rocky Cole, Ziv Epstein, Kiran Garimella, Andrew Gully, Jackson G. Lu, Robert M. Ross, Michael N. Stagnaro, Yunhao Zhang, Gordon Pennycook, David G. Rand
Journal: Nature Human Behaviour (2023)
Dual intron-targeted CRISPR-Cas9-mediated disruption of the AML RUNX1-RUNX1T1 fusion gene effectively inhibits proliferation and decreases tumor volume in vitro and in vivo
Authors: Signe Neldeborg, Johannes Frasez Soerensen, Charlotte Thornild Møller, Marie Bill, Zongliang Gao, Rasmus O. Bak, Kasper Holm, Boe Sorensen, Mette Nyegaard, Yonglun Luo, Peter Hokland, Magnus Stougaard, Maja Ludvigsen, Christian Kanstrup Holm
Journal: Leukemia (2023)

Oncogenic fusion drivers are common in hematological cancers and are thus relevant targets of future CRISPR-Cas9-based treatment strategies. However, breakpoint-location variation in patients pose a challenge to traditional breakpoint-targeting CRISPR-Cas9-mediated disruption strategies. Here we present a new dual intron-targeting CRISPR-Cas9 treatment strategy, for targeting t(8;21) found in 5-10% of de novo acute myeloid leukemia (AML), which efficiently disrupts fusion genes without prior identification of breakpoint location. We show in vitro growth rate and proliferation reduction by 69 and 94% in AML t(8;21) Kasumi-1 cells, following dual intron-targeted disruption of RUNX1-RUNX1T1 compared to a non t(8;21) AML control. Furthermore, mice injected with RUNX1-RUNX1T1-disrupted Kasumi-1 cells had in vivo tumor growth reduction by 69 and 91% compared to controls. Demonstrating the feasibility of RUNX1-RUNX1T1 disruption, these findings were substantiated in isolated primary cells from a patient diagnosed with AML t(8;21). In conclusion, we demonstrate proof-of-principle of a dual intron-targeting CRISPR-Cas9 treatment strategy in AML t(8;21) without need for precise knowledge of the breakpoint location.
Pathophysiology of the right ventricle in health and disease: an update
Authors: Khodr Tello, Robert Naeije, Frances de Man, Marco Guazzi
Journal: Cardiovascular Research (2023)

Abstract The contribution of the right ventricle (RV) to cardiac output is negligible in normal resting conditions when pressures in the pulmonary circulation are low. However, the RV becomes relevant in healthy subjects during exercise and definitely so in patients with increased pulmonary artery pressures both at rest and during exercise. The adaptation of RV function to loading rests basically on an increased contractility. This is assessed by RV end-systolic elastance (Ees) to match afterload assessed by arterial elastance (Ea). The system has reserve as the Ees/Ea ratio or its imaging surrogate ejection fraction has to decrease by more than half, before the RV undergoes an increase in dimensions with eventual increase in filling pressures and systemic congestion. RV-arterial uncoupling is accompanied by an increase in diastolic elastance. Measurements of RV systolic function but also of diastolic function predict outcome in any cause pulmonary hypertension and heart failure with or without preserved left ventricular ejection fraction. Pathobiological changes in the overloaded RV include a combination of myocardial fibre hypertrophy, fibrosis and capillary rarefaction, a titin phosphorylation-related displacement of myofibril tension–length relationships to higher pressures, a metabolic shift from mitochondrial free fatty acid oxidation to cytoplasmic glycolysis, toxic lipid accumulation, and activation of apoptotic and inflammatory signalling pathways. Treatment of RV failure rests on the relief of excessive loading.
Few In-Network Psychiatrists Under Medicare Advantage
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Concerns About a Frailty Screening Initiative and Postoperative Mortality—Reply
Authors: Patrick R. Varley, Dan Buchanan, Daniel E. Hall
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Incidence and Characteristics in Children with Post–COVID-19 Condition in Sweden
Authors: Maria Bygdell, Jenny M. Kindblom, Jari Martikainen, Huiqi Li, Fredrik Nyberg
Journal: JAMA Network Open (2023)

This cohort study of health data from 2 regions in Sweden examines incidence rates of post–COVID-19 among children and compares incidence rates by demographic and clinical characteristics.
Reply to: Concerns about using a digital mask to safeguard patient privacy
Authors: Yahan Yang, Junfeng Lyu, Ruixin Wang, Feng Xu, Qionghai Dai, Haotian Lin
Journal: Nature Medicine (2023)

Due to the entanglement of disease-relevant features with identifiable features of patients when using facial imaging, our original article developed a new technology, called a digital mask (DM), which is based on three-dimensional reconstruction and deep learning algorithms to minimize the risk of patient identification while enabling clinical diagnoses 1 .For validation, we designed experiments involving quantitative evaluation, diagnostic comparisons, reidentification by humans, AI-powered reidentification, and investigation of the level of patient satisfaction with the DM.Potential AI-powered attacks can be in various forms and as the DM is a new technique, such attacks cannot be fully considered in an initial publication.Therefore, we prioritized simulating attacks using publicly available face recognition systems, which are typically trained on RGB (red, green and blue) images.While we appreciate the work of Meeus et al. in proposing the possibility of a Mask2Mask attack for further testing of the DM technique, we think that the methodology used by Meeus et al. is not very relevant to the real-world situation.Specifically, we think that their experiments are not rigorous enough in three aspects.First, the dataset used by Meeus et al. is not comparable to the one used in the original publication.Meeus et al. used retrospectively selected images of people in a non-medical setting, whereas the database we used contained images that had been prospectively collected in clinical settings, which are more suitable for clinical validation.Second, Meeus et al.'s Mask2Mask experiments are based on the assumption that both the algorithm and the face model (the parametric model that represents a three-dimensional face as shape and motion vectors) are known by the attackers, so that the masks in the query image and in the database are the same (a within-mask attack).However, in a real-world application, although the algorithm would be public, the face model can be made private for each institution, such that the most likely type of attack is a cross-mask attack, rather than a within-mask attack.Third, in the experimental setup of the Mask2Mask
Alzheimer Drug Lecanemab Gains Traditional FDA Approval
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Errors in Data Reported in Meta-Analysis on Opioid Agonist Treatment and Mortality
Authors: Thomas Santo
Journal: JAMA Psychiatry (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Clinical benefit and safety associated with mRNA vaccines for advanced solid tumors: A meta‐analysis
Authors: Tian‐yi Zhang, Hang Xu, Xiao‐nan Zheng, Xing‐yu Xiong, Shi‐yu Zhang, Xian‐yanling Yi, Jin Li, Qiang Wei, Jian‐zhong Ai
Journal: MedComm (2023)

Abstract Tumor mRNA vaccines have been developed for over 20 years. Whether mRNA vaccines could promote a clinical benefit to advanced cancer patients is highly unknown. PubMed and Embase were retrieved from January 1, 2000 to January 4, 2023. Random effects models were employed. Clinical benefit (objective response rate [ORR], disease control rate [DCR], 1‐year/2‐year progression‐free survival [PFS], and overall survival [OS]) and safety (vaccine‐related grade 3–5 adverse events [AEs]) were evaluated. Overall, 984 patients (32 trials) were enrolled. The most typical cancer types were melanoma (13 trials), non‐small cell lung cancer (5 trials), renal cell carcinoma (4 trials), and prostate adenocarcinoma (4 trials). The pooled ORR and DCR estimates were 10.0% (95%CI, 4.6–17.0%) and 34.6% (95%CI, 24.1–45.9%). The estimates for 1‐year and 2‐year PFS were 38.4% (95%CI, 24.8−53.0%) and 20.0% (95%CI, 10.4–31.7%), respectively. The estimates for 1‐year and 2‐year OS were 75.3% (95%CI, 62.4–86.3%) and 45.5% (95%CI, 34.0–57.2%), respectively. The estimate for vaccine‐related grade 3–5 AEs was 1.0% (95%CI, 0.2–2.4%). Conclusively, mRNA vaccines seem to demonstrate modest clinical response rates, with acceptable survival rates and rare grade 3–5 AEs.
Oncogenic Drivers and Therapeutic Vulnerabilities in KRAS Wild-Type Pancreatic Cancer
Authors: Harshabad Singh, Rachel B. Keller, Kevin S. Kapner, Julien Dilly, Srivatsan Raghavan, Chen Yuan, Elizabeth F. Cohen, Michael Tolstorukov, Elizabeth Andrews, Lauren K. Brais, Annacarolina da Silva, Kimberly Perez, Douglas A. Rubinson, Rishi Surana, Marios Giannakis, Kimmie Ng, Thomas E. Clancy, Matthew B. Yurgelun, Benjamin L. Schlechter, Jeffrey W. Clark, Geoffrey I. Shapiro, Michael H. Rosenthal, Jason L. Hornick, Valentina Nardi, Yvonne Y. Li, Hersh Gupta, Andrew D. Cherniack, Matthew Meyerson, James M. Cleary, Jonathan A. Nowak, Brian M. Wolpin, Andrew J. Aguirre
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Approximately 8% to 10% of pancreatic ductal adenocarcinomas (PDAC) do not harbor mutations in KRAS. Understanding the unique molecular and clinical features of this subset of pancreatic cancer is important to guide patient stratification for clinical trials of molecularly targeted agents. Experimental Design: We analyzed a single-institution cohort of 795 exocrine pancreatic cancer cases (including 785 PDAC cases) with a targeted multigene sequencing panel and identified 73 patients (9.2%) with KRAS wild-type (WT) pancreatic cancer. Results: Overall, 43.8% (32/73) of KRAS WT cases had evidence of an alternative driver of the MAPK pathway, including BRAF mutations and in-frame deletions and receptor tyrosine kinase fusions. Conversely, 56.2% of cases did not harbor a clear MAPK driver alteration, but 29.3% of these MAPK-negative KRAS WT cases (12/41) demonstrated activating alterations in other oncogenic drivers, such as GNAS, MYC, PIK3CA, and CTNNB1. We demonstrate potent efficacy of pan-RAF and MEK inhibition in patient-derived organoid models carrying BRAF in-frame deletions. Moreover, we demonstrate durable clinical benefit of targeted therapy in a patient harboring a KRAS WT tumor with a ROS1 fusion. Clinically, patients with KRAS WT tumors were significantly younger in age of onset (median age: 62.6 vs. 65.7 years; P = 0.037). SMAD4 mutations were associated with a particularly poor prognosis in KRAS WT cases. Conclusions: This study defines the genomic underpinnings of KRAS WT pancreatic cancer and highlights potential therapeutic avenues for future investigation in molecularly directed clinical trials. See related commentary by Kato et al., p. 4527
Author Correction: Neoantigen-specific stem cell memory-like CD4+ T cells mediate CD8+ T cell-dependent immunotherapy of MHC class II-negative solid tumors
Authors: Spencer E. Brightman, Angelica Becker, Rukman R. Thota, Martin S. Naradikian, Leila Chihab, Karla Soria Zavala, Ashmitaa Logandha Ramamoorthy Premlal, Ryan Q. Griswold, Joseph S. Dolina, Ezra E. W. Cohen, Aaron M. Miller, Bjoern Peters, Stephen P. Schoenberger
Journal: Nature Immunology (2023)